The therapeutic potentials of silibinin – a phytochemical isolated from milk thistle plants – have not been fully realized due to its poor oral bioavailability caused by the low aqueous solubility. Existing solubility enhancement strategies of silibinin by nanonization were limited by their low payload. Herein we developed a supersaturating delivery system of silibinin exhibiting a high payload (≈ 76%) in the form of amorphous silibinin–chitosan nanoparticle complex (or silibinin nanoplex in short) prepared by self-assembly drug-polysaccharide complexation. The effects of (1) pH and (2) charge ratio of chitosan to silibinin on the nanoplex's physical characteristics (i.e. size, zeta potential, and payload) and preparation efficiency (i.e. silibinin utilization, overall yield) were investigated. The formation of nanoplex (≈ 240 nm) was feasible only in a narrow pH range (5.1–5.8) and favored charge ratio below unity. At the optimal condition (pH 5.8 and charge ratio of 0.30), the nanoplex preparation exhibited 87% silibinin utilization rate and 63% yield signifying its high efficiency. The amorphous state and colloidal stabilities of the nanoplex during storage, and prolonged supersaturation generation (3 h) at more than 10 × of the saturation solubility were successfully demonstrated.